# Deep Learning Methods for Small Molecule Drug Discovery: A Survey

arXiv: https://arxiv.org/abs/2303.00313 · HTML: https://mlsanity.com/paper/2303.00313/

## Key facts

- Cited by 10 papers in the map (data through 14 Oct 2026).
- Builds on 92 of its 192 references that are in the map.
- First posted on arXiv 1 Mar 2023.

## Builds on (most cited first, 30 of 92)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [RoBERTa: A Robustly Optimized BERT Pretraining Approach](https://mlsanity.com/paper/1907.11692/) (2019)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Neural Machine Translation by Jointly Learning to Align and Translate](https://mlsanity.com/paper/1409.0473/) (2014)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Neural Message Passing for Quantum Chemistry](https://mlsanity.com/paper/1704.01212/) (2017)
- [On the Properties of Neural Machine Translation: Encoder-Decoder Approaches](https://mlsanity.com/paper/1409.1259/) (2014)
- [Learning deep representations by mutual information estimation and maximization](https://mlsanity.com/paper/1808.06670/) (2018)
- [Graph Contrastive Learning with Augmentations](https://mlsanity.com/paper/2010.13902/) (2020)
- [Deep Graph Infomax](https://mlsanity.com/paper/1809.10341/) (2018)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Strategies for Pre-training Graph Neural Networks](https://mlsanity.com/paper/1905.12265/) (2019)
- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [Semi-Supervised Learning with Deep Generative Models](https://mlsanity.com/paper/1406.5298/) (2014)
- [Deep Neural Networks and Tabular Data: A Survey](https://mlsanity.com/paper/2110.01889/) (2021)
- [InfoGraph: Unsupervised and Semi-supervised Graph-Level Representation Learning via Mutual Information Maximization](https://mlsanity.com/paper/1908.01000/) (2019)
- [Graph Convolutional Policy Network for Goal-Directed Molecular Graph Generation](https://mlsanity.com/paper/1806.02473/) (2018)
- [ChemBERTa: Large-Scale Self-Supervised Pretraining for Molecular Property Prediction](https://mlsanity.com/paper/2010.09885/) (2020)
- [Graph Neural Networks with Learnable Structural and Positional Representations](https://mlsanity.com/paper/2110.07875/) (2021)
- [GraphAF: a Flow-based Autoregressive Model for Molecular Graph Generation](https://mlsanity.com/paper/2001.09382/) (2020)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [Molecular De Novo Design through Deep Reinforcement Learning](https://mlsanity.com/paper/1704.07555/) (2017)
- [Pre-training Molecular Graph Representation with 3D Geometry](https://mlsanity.com/paper/2110.07728/) (2021)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Molecular Transformer - A Model for Uncertainty-Calibrated Chemical Reaction Prediction](https://mlsanity.com/paper/1811.02633/) (2018)
- [Hierarchical Generation of Molecular Graphs using Structural Motifs](https://mlsanity.com/paper/2002.03230/) (2020)
- [Optimization of Molecules via Deep Reinforcement Learning](https://mlsanity.com/paper/1810.08678/) (2018)
- [Why do tree-based models still outperform deep learning on tabular data?](https://mlsanity.com/paper/2207.08815/) (2022)
- [Learning to Plan Chemical Syntheses](https://mlsanity.com/paper/1708.04202/) (2017)

## Built on by (most cited first, 10 of 10)

- [Empowering Molecule Discovery for Molecule-Caption Translation with Large Language Models: A ChatGPT Perspective](https://mlsanity.com/paper/2306.06615/) (2023)
- [Expressivity and Generalization: Fragment-Biases for Molecular GNNs](https://mlsanity.com/paper/2406.08210/) (2024)
- [Small Molecule Optimization with Large Language Models](https://mlsanity.com/paper/2407.18897/) (2024)
- [Accelerating Drug Discovery Through Agentic AI: A Multi-Agent Approach to Laboratory Automation in the DMTA Cycle](https://mlsanity.com/paper/2507.09023/) (2025)
- [A Review on Fragment-based De Novo 2D Molecule Generation](https://mlsanity.com/paper/2405.05293/) (2024)
- [Advancements in Molecular Property Prediction: A Survey of Single and Multimodal Approaches](https://mlsanity.com/paper/2408.09461/) (2024)
- [READ: A Retrieval-Alignment Diffusion Framework for Structure-based Drug Design](https://mlsanity.com/paper/2506.14488/) (2025)
- [Structure-Aware Compound-Protein Affinity Prediction via Graph Neural Networks with Group Lasso Regularization](https://mlsanity.com/paper/2507.03318/) (2025)
- [Revisiting the Disequilibrium Issues in Tackling Heart Disease Classification Tasks](https://mlsanity.com/paper/2407.20249/) (2024)
- [An Integrated Fusion Framework for Ensemble Learning Leveraging Gradient Boosting and Fuzzy Rule-Based Models](https://mlsanity.com/paper/2511.08077/) (2025)

## Abstract (arXiv)

With the development of computer-assisted techniques, research communities including biochemistry and deep learning have been devoted into the drug discovery field for over a decade. Various applications of deep learning have drawn great attention in drug discovery, such as molecule generation, molecular property prediction, retrosynthesis prediction, and reaction prediction. While most existing surveys only focus on one of the applications, limiting the view of researchers in the community. In this paper, we present a comprehensive review on the aforementioned four aspects, and discuss the relationships among different applications. The latest literature and classical benchmarks are presented for better understanding the development of variety of approaches. We commence by summarizing the molecule representation format in these works, followed by an introduction of recent proposed approaches for each of the four tasks. Furthermore, we review a variety of commonly used datasets and evaluation metrics and compare the performance of deep learning-based models. Finally, we conclude by identifying remaining challenges and discussing the future trend for deep learning methods in drug discovery.